Proniosomal transdermal therapeutic system of losartan potassium: development and pharmacokinetic evaluation

Abstract

The purpose of the current study was to investigate the feasibility of proniosomes as transdermal drug delivery system for losartan potassium. Different preparations of proniosomes were fabricated using different nonionic surfactants, such as Span 20, Span 40, Span 60, Span 80, Tween 20, Tween 40, and Tween 80. Different formulae were prepared and coded as PNG-1 (proniosomal gel-1) to PNG-7. The best in vitro skin permeation profile was obtained with proniosomal formulation PNG-2 in 24 h. The permeability parameters such as flux, permeability coefficient, and enhancement ratio were significant for PNG-2 compared with other formulations (P < 0.05). This optimized PNG-2 was fabricated in the form of transdermal patch using HPMC gel as a suitable base. Proniosomal transdermal therapeutic system (PNP-H) was found to be the optimized one as it gave better release of drug and better permeation in a steady-state manner over a desired period of time, that is, 24 h through rat skin. In vivo pharmacokinetic study of PNP-H showed a significant increase in bioavailability (1.93 times) compared with oral formulation of losartan potassium. The formulation appeared to be stable when stored at room temperature (30 +/- 2 degrees C) and at refrigeration temperature (4 +/- 2 degrees C) for 45 days.

A review on novel vesicular drug delivery: proniosomes

“…Ibuprofen (Hu & Rhodes, 1999) Proniosomes (prolonged release for improved anti-inflammatory activity) NSAID 11 Losartan potassium (Thakur et al, 2009 easy storage and handling, increased stability. Encapsulation of drug in niosomal formulations reduces the toxicity in various therapies and applications and also prolongs the encapsulated drug circulation time and changes drug distribution in the body (Azmin et al, 1985;Baillie et al, 1985;Ruckmani et al, 2002).…”

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“…LP proniosomes were formulated by method reported by Thakur et al 6 . Optical microscopy photographs confirmed the successful fabrication of LP proniosomes.…”

“…Formulation of LP proniosomes: LP proniosomes formulated in present study were reported in literature by Thakur et al 6 . Briefly, proniosomes were prepared by mixing the drug with weighed quantities of non-ionic surfactant (Span-60), L-α-lecithin from egg yolk and cholesterol in a wide mouth glass tube ( Table 1).…”

“…Therefore, in order to bypass hepatic first pass metabolism, and reduce its dose, a transdermal formulation can be explored. All these properties, such as extensive hepatic first pass metabolism (67%), short biological half-life (2 h), low dose (25-50 mg), low oral bioavailability (33%), and low molecular weight (461.01 Da), make it good candidate for transdermal drug delivery system [6][7][8][9] . However, TDD is limited by low skin permeability due to the barrier properties of the stratum corneum (SC), the outermost layer of the skin.…”

Enhancing Transdermal Delivery of Glimepiride Via Entrapment in Proniosomal Gel

“…On the other hand, group 4 which treated transdermally with GM loaded proniosomal gel, showed slow hypoglycemic effect and the maximum reduction in the BGL appeared after 6 h (Tmax). The hypoglycemic activity was extended to 24 h by transdermal administration of proniosomal gel loaded with GM compared with the oral administration of GM suspension which terminated after 6 h. 27 Proniosomal GM gel application resulted in 65.34 ± 6.54% (101.68 ± 15.88 mg/dl, reduction in BGL) after 6 h while the inhibition in the BGL produced by the application of GM loaded HPMC gel was 31.71 ± 5.15% after 6 h. The obtained hypoglycemic activity difference between GM loaded proniosomal gel and GM loaded HPMC gel was around two folds. The results confirm the fact that a significant amount of GM was delivered from the proniosomal gel through rat skin to induce the hypoglycemic effect, so it was concluded that proniosomes enhanced drug delivery through the skin, thereby enhance the pharmacological effect.…”